A trial looking at treatment for acute myeloid leukaemia (AML 17)

This trial is looking at the treatment for acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome. There are different parts to this trial that are looking at other types of adult acute myeloid leukaemia (AML) and AML in children. There is information about the other parts of the trial entered separately on CancerHelp UK.

This part of the trial is particularly focusing on those who are under 60 years old, although some people over 60 years old may take part.

Doctors use chemotherapy to treat AML. But chemotherapy by itself may not be enough to get rid of AML. Biological therapies may also work with chemotherapy to treat AML.

We know from research that chemicals called tyrosine kinases signal to cells to start growing and dividing into new cells. Some leukaemia cells have a change (mutation) in the gene called FLT3. This change in the FLT3 gene causes leukaemia cells to make too much tyrosine kinase. Doctors think that a drug that blocks tyrosine kinase called CEP-701 may stop the FLT3 gene making too much tyrosine kinase. And so it may help to stop leukaemia cells from growing and dividing.

Doctors also think that another biological therapy called everolimus may also help people with leukaemia. Everolimus works by stopping a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus may help stop the cancer from growing, or slow it down.

To stop AML coming back doctors may use more chemotherapy. And, if appropriate, they may suggest a bone marrow or stem cell transplant.

Before having the bone marrow or stem cell transplant, you may have more chemotherapy.

The aims of this trial are to

Find out the best dose of daunorubicin
Look at CEP-701 to treat AML
Look at everolimus to treat AML
Compare 2 chemotherapy treatments before a bone marrow transplant
Compare 1 with 2 more cycles of chemotherapy to stop AML coming back

Recruitment

Start 06/04/2009

End 01/07/2014

Phase

Phase 3

Who can enter

You can enter this trial if you

Have acute myeloid Leukaemia (AML)
Are suitable for intensive chemotherapy
Have satisfactory blood test results
Are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant
Are under 60 years of age (older patients can take part if your doctor thinks you are suitable for intensive chemotherapy)

You cannot enter this trial if you

Are in the blast transformation phase
Have already had chemotherapy for your AML (apart from treatment with hydroxycarbamide tablets, or similar low dose treatment, to control your white blood cell count)
Have another type of cancer at the same time as your leukaemia or MDS
Are pregnant or breastfeeding

Trial design

This is a national trial that aims to recruit 2,800 patients with AML and high risk MDS in the UK.

This trial has 2 phases. The first phase is to get rid of the leukaemia (induction phase). The second phase is to stop the leukaemia coming back (consolidation phase). In both phases neither you nor your doctor can choose which treatment you have. This is called randomisation.

At the start of the induction phase you will have daunorubicin.

After the first cycle of chemotherapy, you will have a bone marrow test. This will give the doctor more information about your leukaemia and how it has responded to treatment so far. The doctor will discuss this with you and plan the rest of your treatment. You will be put into 1 of 4 groups.

Group 1
People in this group will continue on to have daunorubicin unless your bone marrow shows you have an abnormal chromosome called 'core binding factor' then you will have 1 dose of Mylotarg as well. Mylotarg is a monoclonal antibody.

Group 2
In this group the leukaemia cells make too much of the chemical tyrosine kinase. So people in this group will be randomised to have of CEP-701 or a dummy treatment (placebo) for 4 doses.

CEP-701, and placebo, is a liquid that you take home to have. You can only mix them with the following fruit juices

Grape
Pineapple
Apple
V8® 100% vegetable juice
Orange juice (smooth only)

You cannot have grapefruit juice while taking CEP-701, or the placebo.

Group 3
People in this group will be randomised to have everolimus or not.

Everolimus is a tablet that you take home to have.

You cannot have grapefruit juice while taking everolimus.

Group 4
In this group, the results of the bone marrow show that there is a high chance your leukaemia may come back after treatment. And the doctor will plan for a bone marrow or stem cell transplant. If you have chemotherapy before your transplant you will be randomised to have one of the following

Fludarabine, Ara-C, G-CSF and idarubicin

Daunorubicin and clorfarabine

You have a bone marrow test after cycle 2 of chemotherapy in groups 1, 2 and 3. If you are in complete remission, then you will go on to have consolidation chemotherapy.

In the consolidation phase everyone will high dose Ara-C, but you will be randomised to have 1 or 2 cycles of treatment.

If you take part in this trial, the researchers will ask your permission to store some of your blood and bone marrow samples. These samples will be stored safely and may be used in the future, but for research purposes only. This is because studying these samples may help researchers learn more about leukaemia.

If you don’t wish to have your blood and bone marrow samples stored for research, you don’t have to. You can still take part in the trial.

Hospital visits

Before you start treatment you will see the doctor and have various tests. These tests will include

Blood tests
Bone marrow tests
Scans

You will have a blood test and possibly a bone marrow test before each cycle of chemotherapy.

All the chemotherapy is given through a drip into a vein; you will probably have these as an outpatient. There is a possibility that some people may need to have their chemotherapy as an inpatient, so may stay overnight in hospital.